The Clinical Studies of the NIMH Collaborative Program on the Psychobiology of Depression involves an interrelated and coordinated group of investigations conducted on two samples drawn from five centers -- mood disordered probands and their relatives. This application seeks to continue the follow-up of the samples and to implement several new, but related aims: 1) Investigation of the long-term course of illness in probands, relatives, spouses, and controls. 2) Determination of predictors of onset and recurrence in the same samples. 3) Investigation of suicidal behavior, mortality, and medical morbidity. 4) Investigation of personality disorders in the samples, including validity, joint familial transmission with mood disorders, and influence on clinical course of mood disorders. 5) A genetic linkage study of unipolar families. 6) Investigation of stability of diagnosis on familial modes of transmission. 7) Further investigation of secular trends in the occurrence of mood disorders. These aims have important public health, clinical, and research implications.